It is hypothesized that the known defects for metabolism of CHO, proteins and lipids in uremia result from an imbalance of some positive and/or negative effectors of key enzymes which regulate these pathways. Imbalances of normally occurring nutrients and metabolites derive from markedly decreased function of kidney tissues, dietary alterations, malnutrition and various compensatory adaptations of these. In this view, the cellular imbalances of nutrients and metabolites, rather than some specific "toxins" adversely effect cell metabolism. This project has 5 objectives: to determine, (1) whether altered modulation of regulatory enzymes by imbalances of normal nutrients, metabolites and trace minerals produce changes in CHO, fat and protein metabolism which characterize uremia; (2) whether limitations in one metabolic pathway effects the response of other pathways; (3) to what extend the metabolic abnormalities are the result of malnutrition per se, rather than uremia; (4) whether (and how) chronic hemodialysis exerts its beneficial effect by modifying (1) and (2); (5) whether dietary amino acid supplements improve CHO, amino acid and fat metabolism and protein synthesis at the cellular level in uremic patients. The metabolism of the circulating leukocyte (neutrophil) resembles that of other nucleated cells. It has been used to study CHO metabolism, protein synthesis, triglyceride metabolism, defects in the urea cycle, as well as chronic malnutrition, carious disease states and inborn errors of metabolism. We propose to use the leukocyte as a cell model to test our hypothesis regarding defective regulation of cell metabolism in uremia, and to study the effects of chronic hemodialysis and amino acid supplementation. Enzyme regulation, energy and triglyceride metabolism, protein and RNA synthesis will be the major modalities studied. The role of cellular amino acid gradients and trace mineral levels also will be examined. Uremic patients in local dialysis programs and non-uremic "control" patients from the OUHSC population will be studied. Data will be computerized for retrieval and biostatistical analysis.